Project Viva: Age 7 DNAm and metals EWAS

Required Packages and functions

# libraries
library(sas7bdat)
library(sva)
library(reshape)
library(ggplot2)
library(gridExtra)
library(knitr)
library(dplyr)
library(kableExtra)
library(tidyverse)
library(minfi)
library(stringr)
library(limma)
library(IlluminaHumanMethylation450kanno.ilmn12.hg19)
library(minfi)
library(DMRcate)
library(UpSetR)
library(reshape)
library(corrplot)
library(factoextra)
library(ENmix)

# loading annotation
anno = getAnnotation(IlluminaHumanMethylation450kanno.ilmn12.hg19)
anno = data.frame(anno)

# loading functions
setwd('/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local')
source('EWAS functions.R')

Load DNAm and pheno data

load("/Users/annebozack/Box/NIEHS-R01 ONES/Methylation Data/Age7Blood_ComBat_Betas_Mvals_filteredProbes_metalAnalaysis.RData")

dim(pDatAge7Metal)
# 333 164

dim(ComBat.Mvalues.Metals)
# 394460    333

rownames(pDatAge7Metal) = pDatAge7Metal$samplename

EWAS

As

DMP_As = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'As_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  23361 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  16750 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.933939 
 
# Number of DMRs identified:   6 

# rm(DMP_As); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
2	113992761	113993313	0.00e+00	552	0.00e+00	0.0000000	8
3	46759437	46759698	0.00e+00	261	0.00e+00	0.0000003	7
1	228395659	228396009	0.00e+00	350	0.00e+00	0.0000007	5
17	1395863	1396123	0.00e+00	260	0.00e+00	0.0000018	5
17	16593581	16593613	1.00e-07	32	1.00e-07	0.0007180	4
17	75315562	75315667	4.63e-05	105	4.63e-05	0.1596525	3

No adjustment for fish consumption

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As/As_log2_manhattan_DMP_adj.png")

As, female

pDatAge7Metal_F = pDatAge7Metal[pDatAge7Metal$female_d == 1,]
pDatAge7Metal_F$race_child2 = as.factor(as.numeric(pDatAge7Metal_F$race_child2))

DMP_As_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'As_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  26064 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  15925 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9033443 
 
# Number of DMRs identified:   4 

rm(DMP_As_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
1	11561496	11561711	0.0e+00	215	0.0e+00	0.0000022	3
2	113992761	113993142	0.0e+00	381	0.0e+00	0.0000018	6
7	76027000	76027101	0.0e+00	101	0.0e+00	0.0000119	3
2	198651075	198651347	6.3e-06	272	6.3e-06	0.0090701	3

No adjustment for fish consumption

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_F/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_F/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_F/As_log2_manhattan_DMP_adj.png")

As, male

pDatAge7Metal_M = pDatAge7Metal[pDatAge7Metal$female_d == 0,]
pDatAge7Metal_M$race_child2 = as.factor(as.numeric(pDatAge7Metal_M$race_child2))

DMP_As_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'As_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  11497 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  14521 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8501198 
 
# Number of DMRs identified:   3 

# rm(DMP_As_M); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
17	47091977	47092178	0	201	0	1.2e-06	4
2	164204627	164205032	0	405	0	5.2e-06	5
5	6755149	6755439	0	290	0	2.1e-05	5

No adjustment for fish consumption

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_M/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_M/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_M/As_log2_manhattan_DMP_adj.png")

Ba

DMP_Ba = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Ba_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  11801 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  11923 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.7860875 
 
# Number of DMRs identified:   3 

rm(DMP_Ba); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
17	6899084	6899577	0.000000	493	0.000000	0.0000000	10
16	1583809	1584118	0.000000	309	0.000000	0.0000083	6
6	32145551	32145654	0.000806	103	0.000806	0.9544043	5

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba/Ba_log2_manhattan_DMP_adj.png")

Ba, female

DMP_Ba_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Ba_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  29651 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  23451 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.216079 

rm(DMP_Ba_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
17	6899084	6899577	0.0000000	493	0.0000000	0.0000000	10
17	37123637	37123949	0.0000000	312	0.0000000	0.0000068	9
2	183943387	183943551	0.0000000	164	0.0000000	0.0000317	5
3	112359487	112359652	0.0000001	165	0.0000001	0.0001519	6
7	94285269	94285329	0.0000446	60	0.0000536	0.2543856	5
1	234367321	234367443	0.0002131	122	0.0002131	0.4978958	2

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_F/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_F/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_F/Ba_log2_manhattan_DMP_adj.png")

Ba, male

DMP_Ba_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Ba_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  25363 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  28150 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.261352 

rm(DMP_Ba_M); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
16	1583809	1584118	0e+00	309	0e+00	0.00e+00	6
19	50194119	50194252	0e+00	133	0e+00	2.30e-06	5
6	29595001	29595335	1e-07	334	1e-07	9.07e-05	8

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_M/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_M/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_M/Ba_log2_manhattan_DMP_adj.png")

Cd

DMP_Cd = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Cd_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  9428 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  11922 
# Adjusted, FDR<0.05:  1 
# Adjusted, pBonf<0.05:  1 
# Adjusted, lambda:  0.8236619 

rm(DMP_Cd); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg07044523	0.26 (0.17 ,0.34)	5.28	0	0.0017741	0.0018	chr1	153514376	S100A5

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
7	158045979	158046166	0.0000000	187	0.0000000	6.10e-06	3
5	23507449	23507656	0.0000000	207	0.0000000	1.43e-05	5
17	46685291	46685448	0.0000000	157	0.0000000	8.55e-05	5
7	27184158	27184188	0.0024888	30	0.0024888	1.00e+00	4

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd/Cd_log2_manhattan_DMP_adj.png")

Cd, female

DMP_Cd_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Cd_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  13276 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  13294 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8195885 
 
# Number of DMRs identified:   7 

# rm(DMP_Cd_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
6	32164926	32165321	0.0000000	395	0.0000000	0.0000000	7
17	46685291	46685448	0.0000000	157	0.0000000	0.0000003	5
6	1624385	1624442	0.0000000	57	0.0000001	0.0002031	2
5	23507449	23507656	0.0000001	207	0.0000001	0.0000961	5
6	88757301	88757392	0.0000001	91	0.0000001	0.0002665	5
11	73357094	73357276	0.0000030	182	0.0000035	0.0064276	6
5	132113754	132113860	0.0158178	106	0.0158178	1.0000000	3

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_F/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_F/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_F/Cd_log2_manhattan_DMP_adj.png")

Cd, male

DMP_Cd_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Cd_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  16666 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  19823 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.072079 

# Number of DMRs identified:   3 

# rm(DMP_Cd_M); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
20	61446961	61447369	0.00e+00	408	0.00e+00	0.0000000	11
7	50518572	50518647	1.80e-06	75	2.70e-06	0.0093850	2
6	28446839	28447087	6.55e-05	248	6.55e-05	0.0989943	2

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_M/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_M/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_M/Cd_log2_manhattan_DMP_adj.png")

Cr

DMP_Cr = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Cr_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  29723 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  23245 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.099732 
 
# Number of identified DMR:  0

rm(DMP_Cr); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
NA	NA	NA	NA	NA	NA	NA	NA

No adjustment for fish consumption

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr/Cr_log2_manhattan_DMP_adj.png")

Cr, female

DMP_Cr_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Cr_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  26701 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  25616 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.219568 
 
# Number of identified DMR:  0

rm(DMP_Cr_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
NA	NA	NA	NA	NA	NA	NA	NA

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_F/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_F/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_F/Cr_log2_manhattan_DMP_adj.png")

Cr, male

DMP_Cr_M = run_wEWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Cr_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  17887 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  12418 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8679592 

# Number of DMRs identified:   1 

rm(DMP_Cr_M); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
17	46685291	46685448	0	157	0	1.05e-05	5

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_M/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_M/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_M/Cr_log2_manhattan_DMP_adj.png")

Cs

DMP_Cs = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Cs_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  16687 
# Unadjusted, FDR<0.05:  4 
# Unadjusted, pBonf<0.05:  2 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  13314 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8363101 
 
# Number of DMRs identified:   4 

rm(DMP_Cs); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
6	32847526	32847845	0.0000000	319	0.0000000	2.50e-06	16
6	33280051	33280228	0.0000000	177	0.0000001	6.02e-05	6
13	47472137	47472429	0.0000000	292	0.0000001	5.48e-05	10
20	57427729	57427762	0.0124658	33	0.0124658	1.00e+00	3

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs/Cs_log2_manhattan_DMP_adj.png")

Cs, female

DMP_Cs_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Cs_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  25871 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  15950 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9510468 
 
# Number of DMRs identified:   4 

rm(DMP_Cs_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
1	200272111	200272215	0	104	0	5.70e-06	3
6	29648378	29648628	0	250	0	2.89e-05	8
20	3145355	3145597	0	242	0	3.76e-05	3
5	78985424	78985592	0	168	0	9.92e-05	9

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_F/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_F/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_F/Cs_log2_manhattan_DMP_adj.png")

Cs, male

DMP_Cs_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Cs_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  15896 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  14066 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8664272 
 
# rm(DMP_Cs_M); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
20	57427442	57427973	0	531	0	0	17

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_M/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_M/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_M/Cs_log2_manhattan_DMP_adj.png")

Cu

DMP_Cu = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Cu_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  10199 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  19919 
# Adjusted, FDR<0.05:  29 
# Adjusted, pBonf<0.05:  7 
# Adjusted, lambda:  1.081857 
 
# Number of DMRs identified:   18 

# rm(DMP_Cu); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg00082497	-0.25 (-0.36 ,-0.15)	-5.32	2.6e-06	0.0361295	1.0000	chr1	32802133	MARCKSL1
cg00116766	0.42 (0.28 ,0.56)	2.04	0.0e+00	0.0010722	0.0018	chr16	9857614	GRIN2A;GRIN2A;GRIN2A
cg00908120	0.51 (0.33 ,0.7)	6.26	1.0e-07	0.0063015	0.0567	chr16	72872925	ZFHX3;ZFHX3
cg02155957	0.38 (0.23 ,0.52)	3.25	6.0e-07	0.0142130	0.2558	chr1	46930731
cg04015129	0.7 (0.44 ,0.96)	4.28	3.0e-07	0.0085878	0.1031	chr10	1058036	GTPBP4
cg04692924	-0.42 (-0.59 ,-0.26)	-6.61	1.0e-06	0.0183556	0.3855	chr1	161720042	DUSP12
cg05051957	-0.45 (-0.63 ,-0.28)	-5.60	4.0e-07	0.0108039	0.1621	chr8	141522459	CHRAC1;CHRAC1
cg05955013	-0.39 (-0.54 ,-0.24)	-6.28	5.0e-07	0.0111376	0.1782	chr17	45056646	RPRML
cg06723863	-0.26 (-0.36 ,-0.15)	-5.98	1.8e-06	0.0289638	0.6994	chr16	68270129	ESRP2;ESRP2
cg07380021	-0.5 (-0.69 ,-0.32)	-5.42	1.0e-07	0.0063015	0.0541	chr1	206755252	RASSF5;RASSF5;RASSF5
cg07831553	0.6 (0.36 ,0.85)	3.37	2.7e-06	0.0361295	1.0000	chr19	48796974
cg08370347	0.51 (0.3 ,0.71)	3.91	1.9e-06	0.0289638	0.7331	chr5	171571793	STK10
cg10145926	0.61 (0.38 ,0.83)	5.31	2.0e-07	0.0073929	0.0813	chr14	95875792	C14orf139
cg10653573	0.82 (0.49 ,1.15)	5.43	1.4e-06	0.0244817	0.5386	chr8	141347297	TRAPPC9;TRAPPC9
cg10923018	0.24 (0.16 ,0.32)	2.75	0.0e+00	0.0028603	0.0145	chr6	31743769	C6orf27
cg11608893	0.61 (0.36 ,0.85)	6.05	1.9e-06	0.0289638	0.7596	chr6	32059542	TNXB
cg12067421	-0.47 (-0.62 ,-0.31)	2.01	0.0e+00	0.0010722	0.0032	chr1	203246482
cg13434714	-0.42 (-0.58 ,-0.26)	-5.77	8.0e-07	0.0168736	0.3206	chr12	6936787	LEPREL2
cg15790767	1.04 (0.66 ,1.42)	3.84	1.0e-07	0.0063015	0.0455	chr6	13431216	GFOD1
cg17143270	0.83 (0.52 ,1.14)	5.74	3.0e-07	0.0093778	0.1313	chr1	91532819
cg18299835	-0.23 (-0.33 ,-0.14)	-4.13	2.0e-06	0.0289638	0.7820	chr19	13207445	NFIX
cg18714712	-0.54 (-0.72 ,-0.36)	-5.97	0.0e+00	0.0010722	0.0030	chr19	49866917	DKKL1;TEAD2
cg19532212	0.49 (0.3 ,0.67)	4.46	3.0e-07	0.0087176	0.1133	chr17	56769430	TEX14;RAD51C;TEX14;RAD51C
cg19842134	-0.29 (-0.4 ,-0.17)	-3.53	9.0e-07	0.0170970	0.3419	chr12	54070591	ATP5G2;ATP5G2
cg20365618	-0.24 (-0.34 ,-0.15)	0.42	1.4e-06	0.0245000	0.5635	chr10	121578384	INPP5F;INPP5F
cg23477849	0.28 (0.19 ,0.38)	4.88	0.0e+00	0.0023982	0.0096	chr19	5698492	LONP1
cg25954729	-0.22 (-0.3 ,-0.14)	-6.34	2.0e-07	0.0064642	0.0646	chr11	66610784	RCE1;C11orf80;RCE1
cg26708724	0.66 (0.41 ,0.91)	6.73	5.0e-07	0.0123375	0.2097	chr4	187509785	FAT1
cg27565067	0.48 (0.31 ,0.65)	6.20	0.0e+00	0.0028603	0.0172	chr17	149484	RPH3AL

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
22	45704901	45705265	0.0e+00	364	0.0e+00	0.0000000	7
20	35169538	35169886	0.0e+00	348	0.0e+00	0.0000000	6
16	66304366	66304585	0.0e+00	219	0.0e+00	0.0000001	3
10	121578136	121578639	0.0e+00	503	0.0e+00	0.0000001	4
12	54070516	54070610	0.0e+00	94	0.0e+00	0.0000007	5
16	8806530	8806756	0.0e+00	226	0.0e+00	0.0000004	7
17	149483	149488	0.0e+00	5	0.0e+00	0.0001511	2
6	1604012	1604212	0.0e+00	200	0.0e+00	0.0000158	5
20	3052114	3052483	0.0e+00	369	0.0e+00	0.0000229	9
17	1395863	1396123	0.0e+00	260	0.0e+00	0.0000413	5
19	55660590	55660625	0.0e+00	35	0.0e+00	0.0003111	4
2	130345204	130345405	1.0e-07	201	1.0e-07	0.0001057	3
15	100048370	100048500	1.0e-07	130	1.0e-07	0.0001709	3
17	47091977	47092178	1.0e-07	201	1.0e-07	0.0001289	4
19	50194119	50194252	1.0e-07	133	1.0e-07	0.0002880	5
13	100310161	100310405	1.0e-07	244	1.0e-07	0.0001625	4
11	19736149	19736333	1.0e-07	184	1.0e-07	0.0002511	5
1	207082827	207082900	1.3e-06	73	1.3e-06	0.0067921	2

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu/Cu_log2_manhattan_DMP_adj.png")

Cu, female

DMP_Cu_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Cu_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  19233 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  16219 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9599566 
 
# Number of DMRs identified:   11 
   # chr     start       end            p length          fdr        sidak nprobe
# 1    5    191295    191806 2.084698e-12    511 2.293168e-11 1.609231e-09      9
# 2    6  32063990  32064810 4.914157e-12    820 2.702787e-11 2.363960e-09     30
# 3   15  81426346  81426610 1.166735e-10    264 4.278029e-10 1.743297e-07      7
# 4   11  73357094  73357396 3.201810e-08    302 8.804977e-08 4.181985e-05      7
# 5    2  74875226  74875536 5.410336e-08    310 1.190274e-07 6.884154e-05      7
# 6   21  37442288  37442476 1.402076e-07    188 2.309027e-07 2.941391e-04      3
# 7    1 120174148 120174361 1.507576e-07    213 2.309027e-07 2.791527e-04      2
# 8   17   1395863   1396123 1.679292e-07    260 2.309027e-07 2.547420e-04      5
# 9    8  95962351  95962383 2.534889e-06     32 3.098197e-06 3.076414e-02      4
# 10   6  31734191  31734401 3.970020e-05    210 4.367022e-05 7.186081e-02      6
# 11  19  23941312  23941438 1.175697e-04    126 1.175697e-04 3.079446e-01      3

# rm(DMP_Cu_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
5	191295	191806	0.0000000	511	0.0000000	0.0000000	9
6	32063990	32064810	0.0000000	820	0.0000000	0.0000000	30
15	81426346	81426610	0.0000000	264	0.0000000	0.0000002	7
11	73357094	73357396	0.0000000	302	0.0000001	0.0000418	7
2	74875226	74875536	0.0000001	310	0.0000001	0.0000688	7
21	37442288	37442476	0.0000001	188	0.0000002	0.0002941	3
1	120174148	120174361	0.0000002	213	0.0000002	0.0002792	2
17	1395863	1396123	0.0000002	260	0.0000002	0.0002547	5
8	95962351	95962383	0.0000025	32	0.0000031	0.0307641	4
6	31734191	31734401	0.0000397	210	0.0000437	0.0718608	6
19	23941312	23941438	0.0001176	126	0.0001176	0.3079446	3

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_F/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_F/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_F/Cu_log2_manhattan_DMP_adj.png")

Cu, male

DMP_Cu_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Cu_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  8255 
# Unadjusted, FDR<0.05:  32 
# Unadjusted, pBonf<0.05:  5 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  12165 
# Adjusted, FDR<0.05:  46 
# Adjusted, pBonf<0.05:  13 
# Adjusted, lambda:  0.7385324 

# Number of DMRs identified:   13 

# rm(DMP_Cu_M); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg00908120	0.7 (0.45 ,0.95)	6.29	1.0e-07	0.0036055	0.0505	chr16	72872925	ZFHX3;ZFHX3
cg01007589	0.93 (0.61 ,1.26)	4.79	1.0e-07	0.0024477	0.0282	chr19	49894178	CCDC155
cg01063965	-0.27 (-0.38 ,-0.17)	-6.44	3.0e-07	0.0080101	0.1323	chr11	695461	TMEM80;TMEM80;DEAF1;DEAF1
cg01447660	0.38 (0.22 ,0.53)	-0.92	4.3e-06	0.0399576	1.0000	chr2	69152678
cg01485439	0.5 (0.31 ,0.69)	3.65	8.0e-07	0.0143550	0.3169	chr11	67225937	CABP4
cg02155957	0.48 (0.29 ,0.67)	3.22	1.6e-06	0.0203703	0.6165	chr1	46930731
cg02196294	-0.26 (-0.37 ,-0.15)	-5.41	5.0e-06	0.0450418	1.0000	chr6	39197260	KCNK5
cg02490920	0.37 (0.23 ,0.51)	1.34	4.0e-07	0.0080101	0.1437	chr3	50304406	SEMA3B;SEMA3B
cg02968175	0.31 (0.19 ,0.42)	5.76	4.0e-07	0.0080101	0.1386	chr16	4690020	MGRN1;MGRN1;MGRN1;MGRN1
cg03717239	0.3 (0.18 ,0.42)	0.51	2.6e-06	0.0277414	1.0000	chr8	145574318
cg04015129	0.84 (0.56 ,1.13)	4.27	0.0e+00	0.0010730	0.0097	chr10	1058036	GTPBP4
cg04406071	-0.3 (-0.41 ,-0.19)	-6.07	4.0e-07	0.0080101	0.1442	chr17	59489784	C17orf82
cg04692924	-0.6 (-0.83 ,-0.36)	-6.58	1.1e-06	0.0160189	0.4165	chr1	161720042	DUSP12
cg05051957	-0.61 (-0.85 ,-0.37)	-5.61	1.7e-06	0.0203703	0.6518	chr8	141522459	CHRAC1;CHRAC1
cg05955013	-0.48 (-0.67 ,-0.29)	-6.30	2.1e-06	0.0238012	0.8092	chr17	45056646	RPRML
cg07380021	-0.68 (-0.9 ,-0.46)	-5.43	0.0e+00	0.0008408	0.0025	chr1	206755252	RASSF5;RASSF5;RASSF5
cg08329655	-0.43 (-0.6 ,-0.26)	-5.88	1.2e-06	0.0169324	0.4680	chr11	7534677	PPFIBP2
cg08459368	0.59 (0.36 ,0.82)	2.70	1.0e-06	0.0160189	0.4117	chr11	61974948	SCGB2A1
cg08760128	0.31 (0.19 ,0.43)	6.73	8.0e-07	0.0143550	0.3302	chr16	4723507	MGRN1;MGRN1;MGRN1;MGRN1
cg10053073	-0.21 (-0.31 ,-0.12)	0.54	5.5e-06	0.0484367	1.0000	chr17	73623182	RECQL5
cg10266648	1.04 (0.68 ,1.41)	5.98	1.0e-07	0.0024477	0.0318	chr2	106560529
cg10923018	0.35 (0.24 ,0.47)	2.73	0.0e+00	0.0006035	0.0012	chr6	31743769	C6orf27
cg11608893	0.95 (0.64 ,1.26)	6.08	0.0e+00	0.0008871	0.0040	chr6	32059542	TNXB
cg12243007	0.45 (0.26 ,0.64)	-0.77	4.5e-06	0.0409168	1.0000	chr17	184018	RPH3AL
cg13434714	-0.67 (-0.86 ,-0.47)	-5.78	0.0e+00	0.0001002	0.0001	chr12	6936787	LEPREL2
cg13989834	0.54 (0.33 ,0.75)	3.14	1.3e-06	0.0181143	0.5253	chr9	134400392	UCK1;UCK1
cg15389183	-0.22 (-0.31 ,-0.13)	-6.19	2.3e-06	0.0264805	0.9268	chr14	102829482	TECPR2;CINP
cg15790767	1.18 (0.69 ,1.66)	3.86	3.8e-06	0.0370497	1.0000	chr6	13431216	GFOD1
cg16068812	-1.01 (-1.42 ,-0.61)	-4.27	2.0e-06	0.0238012	0.8051	chr21	44528396	U2AF1;U2AF1;U2AF1
cg16496814	0.28 (0.17 ,0.39)	5.22	1.2e-06	0.0169324	0.4741	chr11	9778721
cg16656826	0.33 (0.2 ,0.45)	0.14	6.0e-07	0.0126948	0.2539	chr5	159343871	ADRA1B;ADRA1B
cg18670846	0.73 (0.43 ,1.03)	-2.30	3.9e-06	0.0378865	1.0000	chr2	68917482
cg18714712	-0.73 (-0.97 ,-0.48)	-5.95	0.0e+00	0.0010211	0.0082	chr19	49866917	DKKL1;TEAD2
cg19005275	0.68 (0.45 ,0.92)	4.29	0.0e+00	0.0016338	0.0163	chr12	113588263	CCDC42B
cg19532212	0.7 (0.44 ,0.96)	4.42	4.0e-07	0.0080757	0.1534	chr17	56769430	TEX14;RAD51C;TEX14;RAD51C
cg20365618	-0.35 (-0.46 ,-0.23)	0.40	0.0e+00	0.0010211	0.0081	chr10	121578384	INPP5F;INPP5F
cg21373263	0.79 (0.49 ,1.1)	3.29	7.0e-07	0.0137845	0.2895	chr10	126751982	CTBP2;CTBP2
cg21864868	0.66 (0.4 ,0.92)	4.22	9.0e-07	0.0153134	0.3675	chr17	46673002	LOC404266;LOC404266;LOC404266;LOC404266;LOC404266
cg22240394	1.04 (0.62 ,1.46)	6.82	2.6e-06	0.0277414	1.0000	chr3	186211630
cg22286640	-0.78 (-1.1 ,-0.46)	-4.65	3.6e-06	0.0363886	1.0000	chr8	67026828
cg23312431	0.34 (0.2 ,0.47)	-0.37	1.6e-06	0.0203703	0.6357	chr21	45773997	TRPM2
cg23477849	0.39 (0.25 ,0.52)	4.90	1.0e-07	0.0024477	0.0312	chr19	5698492	LONP1
cg24543538	0.83 (0.49 ,1.16)	3.22	2.7e-06	0.0281802	1.0000	chr2	241569846	GPR35
cg25954729	-0.31 (-0.41 ,-0.2)	-6.37	0.0e+00	0.0010211	0.0064	chr11	66610784	RCE1;C11orf80;RCE1
cg26708724	0.97 (0.65 ,1.28)	6.72	0.0e+00	0.0008871	0.0044	chr4	187509785	FAT1
cg27503275	0.43 (0.25 ,0.61)	4.12	5.7e-06	0.0487795	1.0000	chr6	3880016

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
10	121578136	121578846	0.0000000	710	0.0000000	0.0000000	5
22	45704901	45705265	0.0000000	364	0.0000000	0.0000000	7
21	45773781	45773997	0.0000000	216	0.0000000	0.0000008	2
4	24796918	24797176	0.0000000	258	0.0000000	0.0000028	6
19	50194119	50194252	0.0000000	133	0.0000000	0.0000115	5
17	70723226	70723386	0.0000000	160	0.0000000	0.0000390	2
20	35169593	35169886	0.0000000	293	0.0000000	0.0000228	5
3	16216093	16216215	0.0000000	122	0.0000001	0.0001340	4
14	78447480	78447640	0.0000000	160	0.0000001	0.0001027	3
17	78549323	78549371	0.0000001	48	0.0000001	0.0005317	3
17	149483	149488	0.0000001	5	0.0000001	0.0062718	2
12	54070516	54070591	0.0000102	75	0.0000110	0.0521028	4
16	8806752	8806756	0.0028704	4	0.0028704	1.0000000	2

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_M/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_M/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_M/Cu_log2_manhattan_DMP_adj.png")

Hg

DMP_Hg = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Hg_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg')

# Unadjusted, N =  326 
# Unadjusted, p<0.05:  37293 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  326 
# Adjusted, p<0.05:  28324 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.24761 
 
# Number of DMRs identified:   4 

# rm(DMP_Hg); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
17	46681110	46681401	0.0000000	291	0.0000000	0.0000012	6
6	31846768	31847009	0.0000000	241	0.0000000	0.0000145	9
10	131843516	131843725	0.0000023	209	0.0000031	0.0043852	3
3	42977952	42978026	0.0004605	74	0.0004605	0.9141599	2

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg/Hg_log2_manhattan_DMP_adj.png")

Hg, female

DMP_Hg_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Hg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_F')

# Unadjusted, N =  154 
# Unadjusted, p<0.05:  35686 
# Unadjusted, FDR<0.05:  156 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  154 
# Adjusted, p<0.05:  15125 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8835584 

# Number of DMRs identified:   3 

# rm(DMP_Hg_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
12	47219625	47220092	0	467	0	0.00e+00	12
4	165877874	165878136	0	262	0	3.10e-06	6
7	27143234	27143478	0	244	0	4.58e-05	7

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_F/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_F/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_F/Hg_log2_manhattan_DMP_adj.png")

Hg, male

DMP_Hg_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Hg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_M')

# Unadjusted, N =  172 
# Unadjusted, p<0.05:  22412 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  172 
# Adjusted, p<0.05:  26536 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.269744 
 
# Number of DMRs identified:   10 

# rm(DMP_Hg_M); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
6	31846768	31847009	0.0000000	241	0.0000000	0.0000000	9
11	18477152	18477680	0.0000000	528	0.0000000	0.0000000	8
11	18433499	18433887	0.0000000	388	0.0000000	0.0000000	5
5	502290	502571	0.0000000	281	0.0000000	0.0000009	3
6	33282735	33283162	0.0000000	427	0.0000000	0.0000020	20
14	104690039	104690244	0.0000000	205	0.0000000	0.0000089	5
1	147737015	147737207	0.0000001	192	0.0000002	0.0003078	4
1	2345151	2345410	0.0000002	259	0.0000002	0.0002524	8
1	117317981	117318133	0.0009779	152	0.0010866	0.9210590	2
11	368613	368683	0.0015854	70	0.0015854	0.9998691	3

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_M/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_M/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_M/Hg_log2_manhattan_DMP_adj.png")

Mg

DMP_Mg = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Mg_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  18232 
# Unadjusted, FDR<0.05:  1 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  15760 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8766869 
 
# Number of DMRs identified:   4 

# rm(DMP_Mg); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
20	3051953	3052483	0.0e+00	530	0.0e+00	0.0000000	10
2	240196768	240196996	0.0e+00	228	1.0e-07	0.0000647	3
6	31543539	31543686	0.0e+00	147	1.0e-07	0.0001052	8
11	368564	368712	1.6e-06	148	1.6e-06	0.0043050	7

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg/Mg_log2_manhattan_DMP_adj.png")

Mg, female

DMP_Mg_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Mg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  33977 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  20218 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.061758 
 
# Number of DMRs identified:   1 

# rm(DMP_Mg_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
6	10884093	10884140	0.0002934	47	0.0002934	0.9147992	2

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_F/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_F/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_F/Mg_log2_manhattan_DMP_adj.png")

Mg, male

DMP_Mg_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Mg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  9395 
# Unadjusted, FDR<0.05:  7 
# Unadjusted, pBonf<0.05:  5 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  12911 
# Adjusted, FDR<0.05:  3 
# Adjusted, pBonf<0.05:  3 
# Adjusted, lambda:  0.7788244 
 
# Number of DMRs identified:   3 

# rm(DMP_Mg_M); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg13434714	-0.59 (-0.78 ,-0.41)	-5.78	0e+00	0.0016685	0.0017	chr12	6936787	LEPREL2
cg18670846	0.83 (0.55 ,1.1)	-2.30	0e+00	0.0035334	0.0071	chr2	68917482
cg26708724	0.88 (0.57 ,1.18)	6.72	1e-07	0.0073831	0.0221	chr4	187509785	FAT1

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
2	152830504	152830665	0	161	0	4.49e-05	5
17	37123668	37123949	0	281	0	4.39e-05	8
5	23507449	23507656	0	207	0	9.40e-05	5

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_M/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_M/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_M/Mg_log2_manhattan_DMP_adj.png")

Mn

DMP_Mn = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Mn_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  27983 
# Unadjusted, FDR<0.05:  6 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  39522 
# Adjusted, FDR<0.05:  13 
# Adjusted, pBonf<0.05:  3 
# Adjusted, lambda:  1.362045 

# Number of DMRs identified:   8 

# rm(DMP_Mn); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg00808511	0.18 (0.11 ,0.25)	2.86	1.6e-06	0.0495452	0.6441	chr16	52495237	TOX3;TOX3
cg03716590	0.18 (0.11 ,0.25)	5.09	8.0e-07	0.0324264	0.3243	chr7	95435309	DYNC1I1;DYNC1I1;DYNC1I1
cg05613017	0.2 (0.12 ,0.28)	5.33	5.0e-07	0.0226928	0.2042	chr12	65589446	LEMD3;LEMD3
cg09856068	-0.11 (-0.16 ,-0.07)	-4.37	5.0e-07	0.0226928	0.1878	chr5	170878246	FGF18
cg11063328	-0.16 (-0.22 ,-0.1)	-6.02	4.0e-07	0.0226928	0.1593	chr11	18343203	GTF2H1;HPS5;HPS5;HPS5;GTF2H1
cg13834844	-0.1 (-0.14 ,-0.06)	-5.14	1.0e-07	0.0140080	0.0560	chr10	102415320
cg14252211	0.19 (0.13 ,0.26)	5.85	0.0e+00	0.0030032	0.0060	chr1	25919394
cg19407717	0.31 (0.22 ,0.4)	4.03	0.0e+00	0.0000228	0.0000	chr2	1544120	TPO;TPO;TPO;TPO
cg19425870	-0.15 (-0.21 ,-0.09)	-6.46	1.0e-06	0.0366926	0.4036	chr11	3876808	STIM1
cg22586726	0.27 (0.16 ,0.38)	-0.97	1.5e-06	0.0495452	0.6014	chr10	134150542	LRRC27;LRRC27;LRRC27;LRRC27;LRRC27
cg24196240	0.33 (0.21 ,0.45)	5.25	1.0e-07	0.0119610	0.0359	chr21	36096009	NCRNA00160
cg25101184	0.25 (0.15 ,0.34)	3.38	4.0e-07	0.0226928	0.1753	chr14	56231604	RPL13AP3
cg27095984	-0.19 (-0.26 ,-0.12)	5.27	3.0e-07	0.0224715	0.1124	chr13	21652115

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
10	134150488	134150760	0.0000000	272	0.0000000	0.0000000	7
19	21657528	21657756	0.0000000	228	0.0000000	0.0000001	4
16	30572738	30573013	0.0000000	275	0.0000000	0.0000014	5
10	45406680	45406847	0.0000000	167	0.0000000	0.0000580	3
16	73100425	73100510	0.0000000	85	0.0000001	0.0001462	2
20	61659979	61660250	0.0000001	271	0.0000001	0.0000854	2
10	35484767	35484824	0.0001922	57	0.0002197	0.7356060	3
15	91473290	91473365	0.0005497	75	0.0005497	0.9445390	2

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn/Mn_log2_manhattan_DMP_adj.png")

Mn, female

DMP_Mn_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Mn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  28256 
# Unadjusted, FDR<0.05:  3 
# Unadjusted, pBonf<0.05:  3 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  39254 
# Adjusted, FDR<0.05:  3 
# Adjusted, pBonf<0.05:  2 
# Adjusted, lambda:  1.350311 

# Number of DMRs identified:   3 

# rm(DMP_Mn_F); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg11063328	-0.25 (-0.33 ,-0.17)	-6.00	0e+00	0.0008720	0.0009	chr11	18343203	GTF2H1;HPS5;HPS5;HPS5;GTF2H1
cg19425870	-0.24 (-0.31 ,-0.16)	-6.45	0e+00	0.0011946	0.0024	chr11	3876808	STIM1
cg22396353	-0.15 (-0.2 ,-0.09)	-6.10	2e-07	0.0207498	0.0622	chr22	46692687	GTSE1;GTSE1;CN5H6.4

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
16	73100425	73100510	0.0e+00	85	1.0e-07	0.0001673	2
6	3849410	3849690	5.0e-07	280	7.0e-07	0.0006411	10
11	76839190	76839217	4.6e-06	27	4.6e-06	0.0654209	3

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_F/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_F/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_F/Mn_log2_manhattan_DMP_adj.png")

Mn, male

DMP_Mn_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Mn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  14905 
# Unadjusted, FDR<0.05:  27 
# Unadjusted, pBonf<0.05:  9 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  19332 
# Adjusted, FDR<0.05:  32 
# Adjusted, pBonf<0.05:  15 
# Adjusted, lambda:  0.9962195 
# Number of DMRs identified:   12 

rm(DMP_Mn_M); gc()

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_M/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_M/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_M/Mn_log2_manhattan_DMP_adj.png")

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg03425412	-0.23 (-0.31 ,-0.14)	-5.94	7.0e-07	0.0133241	0.2798	chr20	21500337
cg04143120	0.42 (0.28 ,0.55)	6.79	0.0e+00	0.0007642	0.0053	chr11	72968848
cg04885068	0.19 (0.12 ,0.26)	6.47	1.0e-07	0.0024926	0.0306	chr1	9099298	SLC2A5;SLC2A5
cg05041382	-0.12 (-0.17 ,-0.07)	-6.39	2.0e-06	0.0288229	0.7782	chr13	50366546	KPNA3
cg05249026	-0.17 (-0.23 ,-0.11)	-2.36	2.0e-07	0.0045702	0.0777	chr16	11031524	DEXI
cg06051716	0.35 (0.24 ,0.46)	6.49	0.0e+00	0.0003949	0.0024	chr6	169225783
cg06184647	-0.14 (-0.2 ,-0.08)	-5.92	3.7e-06	0.0455095	1.0000	chr16	88450241
cg06756211	-0.2 (-0.27 ,-0.14)	-6.05	0.0e+00	0.0003949	0.0021	chr1	223936799	CAPN2;CAPN2
cg06883949	-0.12 (-0.17 ,-0.08)	-6.47	6.0e-07	0.0122154	0.2443	chr4	1795240	FGFR3;FGFR3;FGFR3
cg08072480	-0.14 (-0.19 ,-0.08)	-6.61	1.8e-06	0.0279544	0.7217	chr11	65292666	SCYL1;SCYL1
cg10088075	-0.11 (-0.16 ,-0.07)	-6.21	3.3e-06	0.0417784	1.0000	chr16	30407103	ZNF48;ZNF48
cg11480534	0.4 (0.24 ,0.55)	5.84	9.0e-07	0.0162120	0.3567	chr11	62255850	AHNAK
cg11521780	-0.14 (-0.18 ,-0.09)	-5.77	0.0e+00	0.0014335	0.0115	chr12	53693949	C12orf10
cg11755803	0.41 (0.25 ,0.57)	5.79	1.4e-06	0.0237384	0.5460	chr12	129000542	TMEM132C
cg12700904	-0.11 (-0.15 ,-0.06)	-5.94	1.8e-06	0.0279544	0.7268	chr3	13590720	FBLN2;FBLN2
cg12828656	-0.15 (-0.2 ,-0.11)	-0.50	0.0e+00	0.0001814	0.0007	chr5	132577108	FSTL4
cg13834844	-0.15 (-0.22 ,-0.09)	-5.13	1.8e-06	0.0279544	0.6946	chr10	102415320
cg13848566	-0.17 (-0.23 ,-0.11)	-6.36	2.0e-07	0.0037872	0.0606	chr9	89561175	GAS1
cg14139125	-0.11 (-0.15 ,-0.06)	-5.83	3.2e-06	0.0417784	1.0000	chr6	170893945	PDCD2;PDCD2
cg14149680	-0.29 (-0.38 ,-0.2)	-6.35	0.0e+00	0.0001169	0.0004	chr11	2187632	TH;TH;TH
cg16560774	-0.17 (-0.23 ,-0.11)	-6.46	0.0e+00	0.0017155	0.0154	chr17	79373381	BAHCC1
cg19407717	0.49 (0.35 ,0.64)	4.03	0.0e+00	0.0000387	0.0001	chr2	1544120	TPO;TPO;TPO;TPO
cg19511862	-0.1 (-0.14 ,-0.07)	-6.26	4.0e-07	0.0094291	0.1697	chr12	125478458	BRI3BP
cg19641404	-0.11 (-0.16 ,-0.07)	-5.87	2.4e-06	0.0340684	0.9539	chr2	232826272	DIS3L2
cg20414082	0.26 (0.16 ,0.36)	3.20	5.0e-07	0.0103493	0.1966	chr1	203002593
cg20504533	-0.22 (-0.28 ,-0.16)	-5.85	0.0e+00	0.0000387	0.0001	chr17	15848253	ADORA2B;ADORA2B
cg22563312	-0.17 (-0.23 ,-0.11)	-6.27	1.0e-07	0.0027236	0.0381	chr5	179334739	TBC1D9B;TBC1D9B
cg22702772	-0.15 (-0.2 ,-0.1)	-6.69	1.0e-07	0.0024926	0.0308	chr3	48699012	CELSR3
cg24196240	0.42 (0.27 ,0.57)	5.27	1.0e-07	0.0031208	0.0468	chr21	36096009	NCRNA00160
cg24948962	-0.22 (-0.29 ,-0.14)	-5.44	1.0e-07	0.0020477	0.0205	chr18	2906032	EMILIN2
cg25152909	0.44 (0.28 ,0.59)	6.08	1.0e-07	0.0024926	0.0324	chr5	172566090	C5orf41
cg25466588	-0.09 (-0.13 ,-0.06)	-5.90	2.8e-06	0.0375151	1.0000	chr3	23958904	NKIRAS1;RPL15

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
1	161008461	161008977	0.00e+00	516	0.00e+00	0.0000000	8
19	21657528	21658001	0.00e+00	473	0.00e+00	0.0000000	5
19	10736005	10736117	0.00e+00	112	0.00e+00	0.0000052	5
20	5485244	5485511	0.00e+00	267	0.00e+00	0.0000026	6
4	79971176	79971432	0.00e+00	256	0.00e+00	0.0000055	4
20	35169593	35169886	0.00e+00	293	0.00e+00	0.0000054	5
1	9099280	9099462	1.00e-07	182	1.00e-07	0.0001508	3
10	45406680	45406847	1.00e-07	167	2.00e-07	0.0003012	3
3	39543966	39544192	2.90e-06	226	3.90e-06	0.0050930	2
15	91473090	91473365	7.70e-06	275	8.70e-06	0.0110277	4
19	12444612	12444741	8.00e-06	129	8.70e-06	0.0240202	5
5	70883064	70883087	2.07e-05	23	2.07e-05	0.2984923	3

Pb

DMP_Pb = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Pb_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  13157 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  17915 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9851719 
 
# Number of DMRs identified:   8 

# rm(DMP_Pb); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
10	135051021	135051581	0e+00	560	0e+00	0.0000000	11
22	45704901	45705265	0e+00	364	0e+00	0.0000000	7
3	130745441	130745685	0e+00	244	1e-07	0.0000532	10
22	19746155	19746368	1e-07	213	1e-07	0.0000952	3
14	104690039	104690244	1e-07	205	1e-07	0.0001426	5
5	23507449	23507656	1e-07	207	1e-07	0.0001951	5
7	155283139	155283424	1e-07	285	1e-07	0.0001464	3
6	2891972	2892152	1e-07	180	1e-07	0.0002542	5

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb/Pb_log2_manhattan_DMP_adj.png")

Pb, female

DMP_Pb_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Pb_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  10571 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  12173 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.7458629 
 
# Number of identified DMR:  0

# rm(DMP_Pb_F); gc()

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_F/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_F/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_F/Pb_log2_manhattan_DMP_adj.png")

Pb, male

DMP_Pb_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Pb_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  18362 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  12544 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8738391 

# Number of DMRs identified:   6 

# rm(DMP_Pb_M); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
6	33084548	33084985	0.0000000	437	0.0000000	0.0000000	12
1	68512649	68513063	0.0000000	414	0.0000000	0.0000008	7
6	31148331	31148748	0.0000000	417	0.0000000	0.0000009	14
22	45704987	45705265	0.0000000	278	0.0000001	0.0000607	5
22	19751653	19751899	0.0000001	246	0.0000001	0.0001654	3
19	55973098	55973234	0.0002477	136	0.0002477	0.5125157	3

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_M/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_M/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_M/Pb_log2_manhattan_DMP_adj.png")

Se

DMP_Se = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Se_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  17270 
# Unadjusted, FDR<0.05:  1 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  19895 
# Adjusted, FDR<0.05:  4 
# Adjusted, pBonf<0.05:  2 
# Adjusted, lambda:  0.9687492 

# Number of DMRs identified:   3 

# rm(DMP_Se); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg08760128	0.21 (0.13 ,0.28)	6.73	2e-07	0.0327152	0.0981	chr16	4723507	MGRN1;MGRN1;MGRN1;MGRN1
cg10145926	0.55 (0.35 ,0.75)	5.31	1e-07	0.0203812	0.0408	chr14	95875792	C14orf139
cg13434714	-0.42 (-0.56 ,-0.28)	-5.77	0e+00	0.0070511	0.0071	chr12	6936787	LEPREL2
cg26708724	0.59 (0.36 ,0.81)	6.73	5e-07	0.0491345	0.1965	chr4	187509785	FAT1

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
19	50194119	50194252	0	133	0	1.26e-05	5
17	47091977	47092178	0	201	0	9.00e-06	4
6	49681177	49681391	0	214	0	6.89e-05	7

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se/Se_log2_manhattan_DMP_adj.png")

Se, female

DMP_Se_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Se_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  26254 
# Unadjusted, FDR<0.05:  9 
# Unadjusted, pBonf<0.05:  2 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  15227 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9131987 
 
# Number of DMRs identified:   5 

# rm(DMP_Se_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
10	38146245	38146671	0.0e+00	426	0.0e+00	0.0000001	9
6	49681177	49681391	0.0e+00	214	0.0e+00	0.0000003	7
10	38299241	38299574	0.0e+00	333	0.0e+00	0.0000053	9
1	236686563	236686804	0.0e+00	241	0.0e+00	0.0000613	4
6	42928055	42928200	7.9e-06	145	7.9e-06	0.0213843	5

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_F/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_F/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_F/Se_log2_manhattan_DMP_adj.png")

Se, male

DMP_Se_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Se_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  15593 
# Unadjusted, FDR<0.05:  42 
# Unadjusted, pBonf<0.05:  12 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  14283 
# Adjusted, FDR<0.05:  28 
# Adjusted, pBonf<0.05:  7 
# Adjusted, lambda:  0.8126609 
 
# Number of DMRs identified:   3 

# rm(DMP_Se_M); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg00908120	0.6 (0.37 ,0.83)	6.29	1.1e-06	0.0298488	0.4477	chr16	72872925	ZFHX3;ZFHX3
cg01007589	0.79 (0.49 ,1.1)	4.79	7.0e-07	0.0210168	0.2732	chr19	49894178	CCDC155
cg01588060	-0.28 (-0.39 ,-0.18)	-5.90	5.0e-07	0.0172784	0.1867	chr6	2245749	GMDS;GMDS
cg04692924	-0.6 (-0.81 ,-0.39)	-6.58	1.0e-07	0.0053838	0.0323	chr1	161720042	DUSP12
cg05051957	-0.66 (-0.87 ,-0.44)	-5.61	0.0e+00	0.0009331	0.0037	chr8	141522459	CHRAC1;CHRAC1
cg06723863	-0.35 (-0.47 ,-0.22)	-5.99	1.0e-07	0.0055617	0.0389	chr16	68270129	ESRP2;ESRP2
cg07380021	-0.51 (-0.72 ,-0.3)	-5.43	3.0e-06	0.0474750	1.0000	chr1	206755252	RASSF5;RASSF5;RASSF5
cg07599133	-0.34 (-0.47 ,-0.2)	-5.96	1.8e-06	0.0428804	0.7290	chr19	35068628	LOC643719
cg08459368	0.52 (0.31 ,0.73)	2.70	2.7e-06	0.0474750	1.0000	chr11	61974948	SCGB2A1
cg08760128	0.28 (0.17 ,0.39)	6.73	1.8e-06	0.0428804	0.7131	chr16	4723507	MGRN1;MGRN1;MGRN1;MGRN1
cg10266648	0.84 (0.5 ,1.19)	5.98	3.0e-06	0.0474750	1.0000	chr2	106560529
cg11443888	0.28 (0.17 ,0.39)	2.36	2.3e-06	0.0434950	0.9134	chr6	44244590	TMEM151B
cg11608893	0.85 (0.56 ,1.14)	6.08	0.0e+00	0.0022825	0.0114	chr6	32059542	TNXB
cg12243007	0.44 (0.27 ,0.61)	-0.77	1.1e-06	0.0298488	0.4290	chr17	184018	RPH3AL
cg12897502	-0.83 (-1.15 ,-0.52)	6.10	6.0e-07	0.0193412	0.2321	chr8	67425316	C8orf46
cg13434714	-0.63 (-0.8 ,-0.45)	-5.78	0.0e+00	0.0000222	0.0000	chr12	6936787	LEPREL2
cg16656826	0.29 (0.17 ,0.4)	0.14	2.2e-06	0.0434950	0.8735	chr5	159343871	ADRA1B;ADRA1B
cg17515932	0.79 (0.47 ,1.12)	4.46	3.2e-06	0.0474750	1.0000	chr7	156190074
cg18377660	0.69 (0.43 ,0.95)	5.65	5.0e-07	0.0172784	0.1901	chr1	57535755	DAB1
cg19005275	0.59 (0.38 ,0.81)	4.29	3.0e-07	0.0111028	0.0999	chr12	113588263	CCDC42B
cg21373263	0.84 (0.57 ,1.11)	3.29	0.0e+00	0.0009331	0.0031	chr10	126751982	CTBP2;CTBP2
cg21864868	0.58 (0.34 ,0.81)	4.22	3.4e-06	0.0474955	1.0000	chr17	46673002	LOC404266;LOC404266;LOC404266;LOC404266;LOC404266
cg22286640	-0.73 (-1.03 ,-0.44)	-4.65	2.2e-06	0.0434950	0.8497	chr8	67026828
cg23994888	-0.52 (-0.73 ,-0.31)	-5.91	2.3e-06	0.0434950	0.9045	chr1	6052642	NPHP4
cg25067702	-0.63 (-0.86 ,-0.4)	-6.40	2.0e-07	0.0079009	0.0632	chr17	70723227	SLC39A11;SLC39A11
cg25469351	1.29 (0.76 ,1.82)	5.96	3.1e-06	0.0474750	1.0000	chr7	6191921	USP42
cg26342676	0.61 (0.36 ,0.86)	4.56	3.0e-06	0.0474750	1.0000	chr14	37639757	SLC25A21;SLC25A21;LOC100129794
cg26708724	1.01 (0.73 ,1.3)	6.72	0.0e+00	0.0000140	0.0000	chr4	187509785	FAT1

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
17	70723226	70723386	0e+00	160	0e+00	0.0000001	2
4	24796918	24797176	0e+00	258	0e+00	0.0000151	6
10	121578383	121578639	2e-07	256	2e-07	0.0002571	3

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_M/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_M/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_M/Se_log2_manhattan_DMP_adj.png")

Zn

DMP_Zn = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Zn_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  12854 
# Unadjusted, FDR<0.05:  1 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  23218 
# Adjusted, FDR<0.05:  13 
# Adjusted, pBonf<0.05:  3 
# Adjusted, lambda:  1.097804 

# Number of DMRs identified:   11 

# rm(DMP_Zn); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg00082497	-0.28 (-0.38 ,-0.18)	-5.32	1.0e-07	0.0129186	0.0269	chr1	32802133	MARCKSL1
cg00908120	0.49 (0.3 ,0.67)	6.26	4.0e-07	0.0197441	0.1382	chr16	72872925	ZFHX3;ZFHX3
cg04015129	0.65 (0.4 ,0.91)	4.28	8.0e-07	0.0273868	0.3108	chr10	1058036	GTPBP4
cg05573434	0.42 (0.26 ,0.57)	-3.15	3.0e-07	0.0175293	0.1052	chr4	7648540	SORCS2
cg06723863	-0.25 (-0.35 ,-0.15)	-5.98	1.6e-06	0.0476390	0.6193	chr16	68270129	ESRP2;ESRP2
cg08459368	0.59 (0.38 ,0.81)	2.65	1.0e-07	0.0129186	0.0388	chr11	61974948	SCGB2A1
cg10653573	0.82 (0.5 ,1.13)	5.43	8.0e-07	0.0273868	0.3279	chr8	141347297	TRAPPC9;TRAPPC9
cg13434714	-0.49 (-0.64 ,-0.33)	-5.77	0.0e+00	0.0012795	0.0013	chr12	6936787	LEPREL2
cg15528091	-0.31 (-0.43 ,-0.19)	-6.36	7.0e-07	0.0273868	0.2933	chr19	18119069	ARRDC2;ARRDC2;ARRDC2
cg16496814	0.21 (0.13 ,0.3)	5.21	6.0e-07	0.0273868	0.2425	chr11	9778721
cg19011752	0.25 (0.15 ,0.34)	-2.54	8.0e-07	0.0273868	0.3286	chr21	45772638	TRPM2
cg23477849	0.26 (0.16 ,0.35)	4.88	2.0e-07	0.0156531	0.0783	chr19	5698492	LONP1
cg25954729	-0.21 (-0.29 ,-0.14)	-6.34	2.0e-07	0.0156531	0.0704	chr11	66610784	RCE1;C11orf80;RCE1

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
12	54070516	54070610	0.0000000	94	0.0000000	0.0000047	5
19	18118799	18119069	0.0000000	270	0.0000000	0.0000090	3
10	124638975	124639260	0.0000000	285	0.0000001	0.0000227	12
4	7648539	7648627	0.0000001	88	0.0000002	0.0002692	2
6	41168800	41169049	0.0000001	249	0.0000002	0.0001710	6
17	79503641	79503877	0.0000001	236	0.0000002	0.0002055	4
8	41655672	41655894	0.0000001	222	0.0000002	0.0002427	4
6	32064145	32064258	0.0000002	113	0.0000003	0.0007474	10
22	45704987	45705042	0.0000002	55	0.0000003	0.0016449	4
20	25129506	25129562	0.0000021	56	0.0000023	0.0149234	5
20	35169593	35169609	0.0095658	16	0.0095658	1.0000000	2

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn/Zn_log2_manhattan_DMP_adj.png")

Zn, female

DMP_Zn_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Zn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_F')

# # Unadjusted, N =  158 
# Unadjusted, p<0.05:  12830 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  17143 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9412223 
 
# Number of DMRs identified:   3 

# rm(DMP_Zn_F); gc()

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
11	73357018	73357396	0.0e+00	378	0.0e+00	0.0000000	8
1	120174148	120174361	9.0e-07	213	1.4e-06	0.0017026	2
10	124638975	124639012	3.2e-06	37	3.2e-06	0.0336353	4

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_F/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_F/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_F/Zn_log2_manhattan_DMP_adj.png")

Zn, male

DMP_Zn_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Zn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  16787 
# Unadjusted, FDR<0.05:  36 
# Unadjusted, pBonf<0.05:  8 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  14737 
# Adjusted, FDR<0.05:  36 
# Adjusted, pBonf<0.05:  3 
# Adjusted, lambda:  0.8766913 
 
# Number of DMRs identified:   16 

# rm(DMP_Zn_M); gc()

FDR-significant DMPs

	logFC_CI	AveExpr	P.Value	adj.P.Val	adj.P.Val.bonf	chr	pos	gene
cg00908120	0.8 (0.52 ,1.07)	6.29	0.0e+00	0.0063443	0.0165	chr16	72872925	ZFHX3;ZFHX3
cg01007589	0.91 (0.55 ,1.27)	4.79	2.0e-06	0.0314161	0.8041	chr19	49894178	CCDC155
cg01447660	0.42 (0.25 ,0.59)	-0.92	3.7e-06	0.0417381	1.0000	chr2	69152678
cg02196294	-0.29 (-0.41 ,-0.17)	-5.41	3.6e-06	0.0414185	1.0000	chr6	39197260	KCNK5
cg02490920	0.39 (0.24 ,0.55)	1.34	1.2e-06	0.0201387	0.4632	chr3	50304406	SEMA3B;SEMA3B
cg02711608	0.54 (0.35 ,0.74)	-2.09	2.0e-07	0.0120512	0.0878	chr19	47287964	SLC1A5;SLC1A5;SLC1A5;SLC1A5
cg02968175	0.33 (0.2 ,0.46)	5.76	7.0e-07	0.0154847	0.2851	chr16	4690020	MGRN1;MGRN1;MGRN1;MGRN1
cg03352332	0.9 (0.57 ,1.24)	5.54	2.0e-07	0.0120512	0.0964	chr3	186360953	FETUB
cg04015129	0.86 (0.55 ,1.18)	4.27	2.0e-07	0.0120512	0.0877	chr10	1058036	GTPBP4
cg04374006	0.26 (0.16 ,0.37)	-0.27	2.9e-06	0.0377171	1.0000	chr19	33556395	RHPN2
cg04406071	-0.32 (-0.45 ,-0.2)	-6.07	7.0e-07	0.0154847	0.2898	chr17	59489784	C17orf82
cg04692924	-0.66 (-0.92 ,-0.41)	-6.58	7.0e-07	0.0154847	0.2942	chr1	161720042	DUSP12
cg05051957	-0.66 (-0.92 ,-0.39)	-5.61	2.3e-06	0.0319338	0.8941	chr8	141522459	CHRAC1;CHRAC1
cg06723863	-0.36 (-0.51 ,-0.22)	-5.99	3.2e-06	0.0406663	1.0000	chr16	68270129	ESRP2;ESRP2
cg07380021	-0.65 (-0.9 ,-0.41)	-5.43	5.0e-07	0.0134172	0.2147	chr1	206755252	RASSF5;RASSF5;RASSF5
cg08760128	0.36 (0.23 ,0.49)	6.73	2.0e-07	0.0120512	0.0686	chr16	4723507	MGRN1;MGRN1;MGRN1;MGRN1
cg10266648	1.04 (0.64 ,1.45)	5.98	1.2e-06	0.0201387	0.4573	chr2	106560529
cg10653573	1.42 (0.91 ,1.93)	5.37	2.0e-07	0.0120512	0.0662	chr8	141347297	TRAPPC9;TRAPPC9
cg10923018	0.31 (0.18 ,0.44)	2.73	3.5e-06	0.0414185	1.0000	chr6	31743769	C6orf27
cg11761483	-0.72 (-0.99 ,-0.45)	-5.60	5.0e-07	0.0134172	0.1942	chr17	70723386	SLC39A11;SLC39A11
cg13434714	-0.84 (-1.04 ,-0.63)	-5.78	0.0e+00	0.0000001	0.0000	chr12	6936787	LEPREL2
cg14230280	1.22 (0.73 ,1.71)	4.28	2.2e-06	0.0314161	0.8482	chr9	132502800	PTGES
cg16496814	0.32 (0.2 ,0.44)	5.22	4.0e-07	0.0134172	0.1415	chr11	9778721
cg16656826	0.34 (0.21 ,0.48)	0.14	2.1e-06	0.0314161	0.8405	chr5	159343871	ADRA1B;ADRA1B
cg17155018	-1.02 (-1.44 ,-0.6)	1.39	4.3e-06	0.0469139	1.0000	chr6	111953066
cg18037826	0.41 (0.25 ,0.57)	4.29	1.1e-06	0.0201387	0.4346	chr12	109273835	DAO
cg19005275	0.75 (0.49 ,1)	4.29	0.0e+00	0.0063443	0.0190	chr12	113588263	CCDC42B
cg19532212	0.76 (0.47 ,1.05)	4.42	5.0e-07	0.0134172	0.2072	chr17	56769430	TEX14;RAD51C;TEX14;RAD51C
cg21373263	0.88 (0.55 ,1.21)	3.29	5.0e-07	0.0134172	0.2067	chr10	126751982	CTBP2;CTBP2
cg22240394	1.22 (0.77 ,1.68)	6.82	4.0e-07	0.0134172	0.1707	chr3	186211630
cg22413938	-0.39 (-0.54 ,-0.23)	-4.56	3.3e-06	0.0406663	1.0000	chr14	78447481
cg23477849	0.38 (0.23 ,0.53)	4.90	1.8e-06	0.0292663	0.7024	chr19	5698492	LONP1
cg23601521	0.8 (0.5 ,1.1)	4.87	5.0e-07	0.0134172	0.2111	chr2	50275179	NRXN1;NRXN1;NRXN1
cg25954729	-0.3 (-0.42 ,-0.19)	-6.37	4.0e-07	0.0134172	0.1746	chr11	66610784	RCE1;C11orf80;RCE1
cg26608798	0.39 (0.23 ,0.56)	0.58	2.8e-06	0.0377171	1.0000	chr16	33853544
cg26708724	0.92 (0.56 ,1.28)	6.72	1.0e-06	0.0198743	0.3975	chr4	187509785	FAT1

DMRs

chr	start	end	p	length	fdr	sidak	nprobe
17	70723226	70723386	0.0000000	160	0.0000000	0.0000021	2
10	121578136	121578639	0.0000000	503	0.0000000	0.0000011	4
14	78447480	78447640	0.0000000	160	0.0000000	0.0000148	3
19	50194119	50194252	0.0000000	133	0.0000000	0.0000199	5
4	24796918	24797176	0.0000000	258	0.0000000	0.0000115	6
4	186732836	186733060	0.0000000	224	0.0000000	0.0000157	7
14	76734326	76734605	0.0000000	279	0.0000000	0.0000225	5
21	45773781	45773997	0.0000000	216	0.0000000	0.0000319	2
5	135416204	135416613	0.0000000	409	0.0000000	0.0000219	9
11	63679431	63679637	0.0000001	206	0.0000002	0.0001797	2
20	62716331	62716606	0.0000001	275	0.0000002	0.0001584	4
17	78549323	78549371	0.0000001	48	0.0000002	0.0011866	3
5	1868136	1868357	0.0000003	221	0.0000004	0.0005635	4
22	45704987	45705042	0.0000017	55	0.0000019	0.0120479	4
5	176755392	176755449	0.0000125	57	0.0000133	0.0826896	2
2	88583556	88583805	0.0001149	249	0.0001149	0.1664579	3

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_M/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_M/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_M/Zn_log2_manhattan_DMP_adj.png")